Ultra-sensitive magnetic assays for sepsis diagnostics

用于脓毒症诊断的超灵敏磁性测定

• 批准号: 7250099
• 负责人: Mark S. DiIorio
• 金额: $ 63.88万
• 依托单位: MAGNESENSORS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-15 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7250099
• 关键词: Antibodies; Area; Aspirate substance; Automation; Bacteria; Beds; Binding; Biological; Biological Assay; Blood; Boston; Clinical; Complex; Data; Data Collection; Detection; Diagnosis; Diagnostic; Diagnostic tests; Early Diagnosis; Escherichia; Escherichia coli; Fingers; Goals; Hospitals; Infection; Intervention; Label; Laboratory Personnel; Lead; Legal patent; Libraries; Life; Liquid substance; Magnetism; Measurement; Measures; Nucleic Acids; Organism; Pathogen detection; Pediatric Hospitals; Performance; Polymerase Chain Reaction; Preparation; Range; Research Ethics Committees; Sampling; Sensitivity and Specificity; Sepsis; Specificity; Specimen; Speed; Staging; Staphylococcus aureus; Surface Antigens; System; Technology; Test Result; Testing; Time; Toxin; Trachea; United States National Institutes of Health; Urine; Whole Organism; base; concept; cost; design; design and construction; improved; innovation; instrument; instrumentation; magnetic field; nanoparticle; next generation; nucleic acid detection; pathogen; programs; prototype; sensor; time use

DESCRIPTION (provided by applicant): The program is aimed at applying an ultra-sensitive magnetic detection platform to the rapid and early diagnosis of pathogens causing sepsis. The technology platform is based on labeling biomolecules with magnetic nanoparticles and detecting the magnetic field generated upon binding using patented ultra-sensitive magnetic sensors. While the initial focus will be on a "proof-of-principle" demonstration for the direct detection of two major pathogens, Staphylococcus aureus and Escherichia coli, responsible for sepsis, the diagnostic platform should be generally applicable to a wide range of pathogens. Direct detection of live bacteria will be demonstrated by measuring the binding of magnetic labeled antibodies to a surface antigen on the target pathogen. Purchased bacteria will first be used to demonstrate a proof-of-concept for high sensitivity in a rapid, "mix and measure" magnetic assay. A next generation prototype instrument will then be produced and placed at our collaborator, Children's Hospital Boston. An existing IRB-approved library of clinical specimens with documented infections (600 blood and urine samples, 150 trachea) aspirates) will be examined in order to demonstrate clinical utility, including sensitivity, specificity and short assay times. The ultimate goal of this program is to show a limit of detection < 100 bacteria/ml in clinical samples with a total (preparation and measurement) assay time of less than 15 minutes. Additionally, detection limits as low as 5-10 bacteria in small samples (e.g., 20 ul) may be possible by using the unique ability to externally manipulate magnetic nanoparticle labels using magnetic fields. Note that magnetic detection is not hampered by measurement in biological fluids and the mix and measure format in microplate wells requires little sample preparation, thereby minimizing errors.

描述（由申请人提供）：该项目旨在应用超灵敏磁检测平台来快速、早期诊断引起败血症的病原体。该技术平台基于用磁性纳米颗粒标记生物分子，并使用获得专利的超灵敏磁传感器检测结合时产生的磁场。 虽然最初的重点将放在直接检测两个主要物质的“原理验证”演示上 病原体，金黄色葡萄球菌和大肠杆菌，导致脓毒症，诊断平台 应普遍适用于多种病原体。 通过测量磁性标记的结合来证明活细菌的直接检测 针对目标病原体表面抗原的抗体。购买的细菌将首先用于 展示了快速“混合和测量”磁性测定中高灵敏度的概念验证。然后将生产下一代原型仪器并将其放置在我们的合作者波士顿儿童医院。将检查现有的 IRB 批准的有感染记录的临床样本库（600 份血液和尿液样本、150 份气管抽吸物），以证明临床实用性，包括敏感性、特异性和短测定时间。 该计划的最终目标是在总（准备和测量）检测时间少于 15 分钟的情况下，显示临床样本中的检测限 < 100 个细菌/ml。此外，通过利用磁场从外部操纵磁性纳米颗粒标签的独特能力，小样品（例如 20 ul）中的检测限可低至 5-10 个细菌。请注意，磁性检测不会受到生物液体测量的阻碍，并且微孔板孔中的混合和测量格式几乎不需要样品制备，从而最大限度地减少错误。